Fig. (2).

Possibilities for combination therapy and the potential optimal point of time to start a specific treatment modality. XO, free radicals and nNOS increase prenatally after hypoxia-ischemia and reach the peak immediately after reperfusion/reoxygenation. Then there is a quick decrease in these three kinds of factors during the first 6h after reperfusion/reoxygenation. However, there is a secondary increase of free radical formation 12h later. Cytokines, iNOS and apoptotic activity appear 3h after reperfusion/reoxygenation and gradually increase to the plateau at 6h. 12h after reperfusion/reoxygenation, the downregulation of trophic factors starts and is stabilized at 24h. Interventions of hypothermia/NOS-inhibitor/2-IB/anti-oxidants/Xenon should be started as early as possible, at least no later than 6h after reperfusion/reoxygenation. Interventions of anti-inflammation and anti-apoptosis should also start early and no later than 9h after reperfusion/reoxygenation. Trophic support with EPO and IGF-1 can be performed 12h after reperfusion/reoxygenation. Furthermore, stem cells are suggested to be carried out 24h later. EPO=erythropoietin; IGF-1=insuline-like growth factor 1; 2-IB=2-iminobiotin; NOS= nitric oxide synthase; nNOS= neuronal NOS; TAT-JBD= TAT coupled JNK binding domain; TAT-NBD=TAT-coupled NFκB essential modulator binding domain; XO=xanthine-oxidase.